Canadian guidance for diagnosis and management of acute hepatic porphyrias.

Acute hepatic porphyrias (AHP) comprise four rare monogenic autosomal conditions. Each is linked to a deficiency of heme metabolizing enzymes. Common manifestations include severe abdominal pain, nausea, confusion, hyponatremia, hypertension, tachycardia, and neuropathy. Diagnosis is challenging due to a non-specific, variable presentation with symptoms mimicking other common conditions. Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, δ-aminolevulinic acid and porphyrins using a single random (spot) sample. However, many patients have complications due to delays in diagnosis and management. A novel small interfering RNA-based agent, givosiran, has demonstrated efficacy in reducing acute attacks in a recent Phase III trial, leading to its approval for the management of AHP. Early diagnosis is crucial for the timely introduction of disease-modifying treatments that reduce impairments, enhance quality of life, and extend survival. In this guidance, we aim to improve awareness and outcomes of AHP by making recommendations about diagnosis, monitoring, and treatment in Canada.

Optimizing Informed Consent Discussions: Developing a Narrative for Transfusion Consent.

Ensuring patient informed consent is a key tenet of modern medicine. Although transfusion of blood products is among the most common medical procedures performed in hospitalized patients, there is evidence that informed consent for transfusion is at times incomplete, poorly understood, hurried, and/or inaccurate. This study aimed to develop a narrative that can be used as a framework for practicing physicians and for educational purposes to optimize the process for obtaining informed consent for blood transfusion. The narrative was developed using a modified Delphi approach with 5 Rounds that included feedback from transfusion medicine (TM) experts, transfusion-provider physicians, and lay people. The surveys collected qualitative and quantitative data analyzed using thematic content analysis and descriptive statistics, respectively. Results from Rounds 1 and 2 generated a draft narrative and Rounds 3 to 5 informed further modifications. Round 1 included draft narrative scripts from 28 TM experts; thematic coding generated 97 topics. In round 2, 22/28 of the initial experts rated items identified from Round 1. Those with a content validity index (CVI) ≥ 0.8 were used by the authors to develop a narrative. In Round 3, 20/24 participants from Round 2 reviewed the narrative with 100% agreeing on the items included and 90% agreeing the flow was logical. In Round 4, 23 transfusion prescribers (non-TM physicians) reviewed the narrative for flow, manner, length, and usability; there was 83% agreement with the nonexclusion of important topics; 91% felt it would be effective for teaching trainees. Round 5 included 24 nonmedical laypeople of different demographics. Most participants (92%) thought that the script was appropriate in length and there were opportunities to ask questions. Participants could also identify the adverse transfusion reactions and understand that they could refuse the transfusion. A narrative for obtaining informed consent for blood transfusion was created through multiple rigorous iterations of review and feedback with both transfusion providers and the lay public. The narrative, developed for a specific clinical scenario, was well-received by medical and nonmedical participants and can be used, and modified, to help ensure patients understand the risks and benefits of blood transfusion.

Transfusion medicine education delivery in Rwanda: Adapting Transfusion Camp to a resource-limited setting.

BACKGROUND: Due to few teaching faculty, resource-limited settings may lack the education curricula providers need for safe practice. As safe surgery becomes an increasing priority worldwide, it is essential to improve access to critical education content including in transfusion medicine. Transfusion Camp is a longitudinal curriculum, shown to increase knowledge in postgraduate trainees. The objective was to develop a sustainable bilateral partnership between Rwanda and Canada, and to integrate Transfusion Camp into the existing curriculum of the School of Medicine and Pharmacy at University of Rwanda. METHODS: A Transfusion Camp pilot course was initiated through collaboration of experts in Rwanda and Canada. Planning occurred over 6 months via online and in-person meetings. Canadian teaching faculty adapted course content via iterative discussion with Rwandan faculty. Final content was delivered through online pre-recorded lectures by Canadian Faculty, and in-person small-group seminars by Rwandan Faculty. Project feasibility was assessed through structured evaluation and informal debriefing. RESULTS: Twenty-seven postgraduate trainees were present for the pilot course, of whom 21 (78%) submitted evaluation forms. While the structure and content of the adapted Transfusion Camp curriculum were well-received, the majority of respondents indicated a preference for in-person rather than pre-recorded lectures. Debriefing determined that future courses should focus on continuing education initiatives aimed at physicians entering or already in independent practice. CONCLUSION: A partnership between universities and blood operators in high-resource and resource-limited countries results in a transfusion medicine curriculum that is locally applicable, multidisciplinary, and supportive of learning benefitting the learners and educators alike.

Development of a national out-of-hospital transfusion protocol: a modified RAND Delphi study.

BACKGROUND: Early resuscitation with blood components or products is emerging as best practice in selected patients with trauma and medical patients; as a result, out-of-hospital transfusion (OHT) programs are being developed based on limited and often conflicting evidence. This study aimed to provide guidance to Canadian critical care transport organizations on the development of OHT protocols. METHODS: The study period was July 2021 to June 2022. We used a modified RAND Delphi process to achieve consensus on statements created by the study team guiding various aspects of OHT in the context of critical care transport. Purposive sampling ensured representative distribution of participants in regard to geography and relevant clinical specialties. We conducted 2 written survey Delphi rounds, followed by a virtual panel discussion (round 3). Consensus was defined as a median score of at least 6 on a Likert scale ranging from 1 ("Definitely should not include") to 7 ("Definitely should include"). Statements that did not achieve consensus in the first 2 rounds were discussed and voted on during the panel discussion. RESULTS: Seventeen subject experts participated in the study, all of whom completed the 3 Delphi rounds. After the study process was completed, a total of 39 statements were agreed on, covering the following domains: general oversight and clinical governance, storage and transport of blood components and products, initiation of OHT, types of blood components and products, delivery and monitoring of OHT, indications for and use of hemostatic adjuncts, and resuscitation targets of OHT. INTERPRETATION: This expert consensus document provides guidance on OHT best practices. The consensus statements should support efficient and safe OHT in national and international critical care transport programs.

Transfusion camp: A retrospective study of self-reported impact on postgraduate trainee transfusion practice.

BACKGROUND: The optimal method of postgraduate transfusion medicine (TM) education remains understudied. One novel approach is Transfusion Camp, a longitudinal 5-day program that delivers TM education to Canadian and international trainees. The purpose of this study was to determine the self-reported impact of Transfusion Camp on trainee clinical practice. STUDY DESIGN AND METHODS: A retrospective analysis of anonymous survey evaluations from Transfusion Camp trainees over three academic years (2018-2021) was conducted. Trainees were asked, "Have you applied any of your learning from Transfusion Camp into your clinical practice?". Through an iterative process, responses were categorized into topics according to program learning objectives. The primary outcome was the rate of self-reported impact of Transfusion Camp on clinical practice. Secondary outcomes were to determine impact based on specialty and postgraduate year (PGY). RESULTS: Survey response rate was 22%-32% over three academic years. Of 757 survey responses, 68% of respondents indicated that Transfusion Camp had an impact on their practice, increasing to 83% on day 5. The most frequent areas of impact included transfusion indications (45%) and transfusion risk management (27%). Impact increased as PGY increased with 75% of PGY-4+ trainees reporting impact. In multivariable analysis, the impact of specialty and PGY varied depending on the objective. DISCUSSION: The majority of trainees report applying learnings from Transfusion Camp to their clinical practice with variations based on PGY and specialty. These findings support Transfusion Camp as an effective means of TM education and help identify high-yield areas and gaps for future curriculum planning.

Plasma transfusion practices: A multicentre electronic audit.

BACKGROUND AND OBJECTIVES: Plasma is often transfused to patients with bleeding or requiring invasive procedures and with abnormal tests of coagulation. Chart audits find half of plasma transfusions unnecessary, resulting in avoidable complications and costs. This multicentre electronic audit was conducted to determine the proportion of plasma transfused without an indication and/or at a sub-therapeutic dose. METHODS: Data were extracted on adult inpatients in 2017 at five academic sites from the hospital electronic chart, laboratory information systems and the Canadian Institute for Health Information Discharge Abstract Database. Electronic criteria for plasma transfusion outside recommended indications were: (1) international normalized ratio (INR) < 1.5 with no to moderate bleeding; (2) INR ≥ 1.5, with no to mild bleeding and no planned procedures; and (3) no INR before or after plasma infusion. Sub-therapeutic dose was defined as ≤2 units transfused. RESULTS: In 1 year, 2590 patients received 6088 plasma transfusions encompassing 11,490 units of plasma occurred at the five sites. 77.7% of events were either outside indications or under-dosed. Of these, 34.8% of plasma orders had no indication identified, and 62% of these occurred in non-bleeding patients and no planned procedure with an isolated elevated INR. 70.7% of transfusions were under-dosed. Most plasma transfusions occurred in the intensive care unit or the operating room. Inter-hospital variability in peri-transfusion testing and dosing was observed. CONCLUSION: The majority of plasma transfusions are sub-optimal. Local hospital culture may be an important driver. Electronic audits, with definitions employed in this study, may be a practical alternative to costly chart audits.

Cold agglutinin disease and COVID-19 requiring therapeutic plasma exchange.

A 70-year-old man with known cold autoimmune haemolytic anaemia was referred to the emergency department with increased shortness of breath on exertion. He had been confirmed positive for non-variant COVID-19 infection 1 week earlier based on nasopharyngeal swab PCR assay. CT thorax demonstrated diffuse patchy bilateral ground glass opacities, consistent with COVID-19 pneumonia. Bloodwork demonstrated severe cold agglutinin mediated haemolytic anaemia. To help stabilise the patient, he was transferred to a tertiary care hospital for urgent therapeutic plasma exchange. Key supportive therapy included folic acid supplementation, ensuring the patient was kept warm and warmed infusions including transfusions via the apheresis machine. The patient made a good recovery following plasma exchange, and his haemoglobin levels remained stable by discharge.

TACO-BEL-3: a feasibility study and a retrospective audit of diuretics for patients receiving blood transfusion at ten hospitals.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related morbidity and mortality. A recently completed pilot trial randomized patients to pre-transfusion furosemide versus placebo but had a slower than expected enrollment rate. We sought to determine whether the lack of recruitment was due to a paucity of eligible patients or excessively restrictive eligibility criteria. MATERIALS AND METHODS: At 10 sites, eligible patients were retrospectively identified by first screening blood bank databases over one month for all transfusion episodes meeting trial inclusion criteria, defined as non-surgical patients receiving single RBC unit transfusions. The age threshold was decreased from 65 to 50 years. The first 10 patients meeting inclusion criteria then underwent detailed chart review for the exclusion criteria. The incidence of TACO and furosemide use was also recorded. RESULTS: At the 10 sites, 11 969 red cell units were transfused over 1 month and 1356 met the inclusion criteria. Of the 100 charts reviewed, 60 (60%) had no exclusion criteria. Active bleeding was the most common reason for ineligibility. There were 813 eligible transfusion episodes. Of the eligible patients, 17 (28·3%) had evidence of congestive heart failure, and furosemide was prescribed in 24 (40%). Despite the use of a lower age threshold, three cases of TACO were detected with an incidence of 3%. CONCLUSION: A large number of transfusion episodes met eligibility criteria. With a 3% incidence of TACO, 50% decrease through the use pre-transfusion furosemide and a target consent rate of 30%, a definitive trial of approximately 3000 patients could be completed within 1 year.

Confounding effect of therapeutic protamine and heparin levels on routine and special coagulation testing.

: The management of a patient with hemophilia undergoing cardiovascular surgery relies on accurate coagulation test results. Both unfractionated heparin (UFH) and protamine sulfate used during cardiac surgery can interfere with factor and inhibitor assays. Here we describe the effects of UFH and protamine sulfate on routine coagulation, factor activity, and inhibitor assays. Pooled normal plasma (PNP) with UFH, PNP with protamine sulfate, PNP with both protamine sulfate and UFH were tested for the activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), UFH anti-Xa, one-stage factor VIII (FVIII) activity, one-stage factor IX (FIX) activity, and Bethesda inhibitor assays for FVIII and FIX. UFH had a dose-dependent effect with TT, aPTT, and PT. On Bethesda inhibitor testing, FIX inhibition was detected at 1 U/ml UFH and 3 U/ml UFH for FVIII. Increasing protamine sulfate concentration in PNP prolonged the PT and aPTT in a dose-dependent manner, decreased FVIII and FIX activity and did not affect TT or UFH anti-Xa. At protamine sulfate doses of at least 200 µg/ml there was weak FVIII and FIX inhibition detected. At lower ratios of protamine sulfate to UFH (0.6 : 1-0.8 : 1), the aPTT decreased, suggesting reversal of UFH. However, at protamine sulfate to UFH ratios of 1.0 : 1 and higher, aPTT prolongation was observed. Inhibition of FVIII and FIX was detected at low ratios of protamine sulfate to UFH (below 0.4 : 1) and disappeared at higher ratios. UFH and protamine sulfate, alone or in combination, impact factor activity and inhibitor testing for both FVIII and FIX. Hence, factor activity and inhibitor assay results should be interpreted with caution when UFH or protamine sulfate are present.

Quality of Widely Available Video Instructional Materials for Point-of-Care Ultrasound-Guided Procedure Training in Internal Medicine.

OBJECTIVES: Many instructional materials for point-of-care ultrasound (US)-guided procedures exist; however, their quality is unknown. This study assessed widely available educational videos for point-of-care US-guided procedures relevant to internal medicine: central venous catheterization, thoracentesis, and paracentesis. METHODS: We searched Ovid MEDLINE, YouTube, and Google to identify videos for point-of-care US-guided paracentesis, thoracentesis, and central venous catheterization. Videos were evaluated with a 5-point scale assessing the global educational value and a checklist based on consensus guidelines for competencies in point-of-care US-guided procedures. RESULTS: For point-of-care US-guided central venous catheterization, 12 videos were found, with an average global educational value score ± SD of 4.5 ± 0.7. Indications to abort the procedure were discussed in only 3 videos. Five videos described the indications and contraindications for performing central venous catheterization. For point-of-care US-guided thoracentesis, 8 videos were identified, with an average global educational value score of 4.0 ± 0.9. Only one video discussed indications to abort the procedure, and 3 videos discussed sterile technique. For point-of-care US-guided paracentesis, 7 videos were included, with an average global educational value score of 4.1 ± 0.9. Only 1 video discussed indications to abort the procedure, and 2 described the location of the inferior epigastric artery. CONCLUSIONS: The 27 videos reviewed contained good-quality general instruction. However, we noted a lack of safety-related information in most of the available videos. Further development of resources is required to teach internal medicine trainees skills that focus on the safety of point-of-care US guidance.

A case report of unusually long lag time between immunotactoid glomerulopathy (itg) diagnosis and diffuse large B-cell lymphoma (DLBCL) development.

BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare cause of proteinuria characterized by organized microtubular deposits in the glomerulus. ITG has been associated with underlying lymphoproliferative disorders and any renal impairment may be reversible with treatment of the concomitant hematologic malignancy. This case is the first reported in literature where diffuse large B cell lymphoma developed two years following the initial ITG diagnosis. CASE PRESENTATION: A 55-year-old woman with a history of well-controlled diabetes mellitus and thalassemia trait presented with proteinuria (830 mg/day) in 2010. Initially, she was managed with renin-angiotensin-aldosterone-system blockade. In 2012, the proteinuria worsened (4.3 g/day) and a renal biopsy showed immunotactoid glomerulopathy (Fig. 1). Despite extensive work up, no lymphoproliferative disorder was initially found. In January 2014, the patient presented with a soft-palate mass found on biopsy to be diffuse large B-cell lymphoma. She received 6 cycles of R-CHOP, 4 cycles of high dose methotrexate chemotherapy for CNS prophylaxis and 30 Gy of Intensity Modulated Radiation Therapy. Follow-up revealed complete remission of diffuse large B-cell lymphoma and resolution of proteinuria from the ITG. CONCLUSION: As we recognize that patients with ITG may develop hematopoietic neoplasms, close long-term monitoring is important. Moreover, treatment of the lymphoproliferative disorder can allow for complete remission of ITG.

How we made professionalism relevant to twenty-first century residents.

The complexity of the current medical trainee work environment, including the impact of social media participation, is underappreciated. Despite rapid adoption of social media by residents and the introduction of social media guidelines targeted at medical professionals, there is a paucity of data evaluating practical methods to incorporate social media into professionalism teaching curricula. We developed a flipped classroom program, focusing on the application of professionalism principles to challenging real-life scenarios including social media-related issues. The pre-workshop evaluation showed that the participants had a good understanding of basic professionalism concepts. A post-workshop survey assessed residents' comfort level with professionalism concepts. The post-workshop survey revealed that the postgraduate trainees perceived significant improvement in their understanding of professionalism (p < 0.05). Resident responses also exposed some challenges of real-life clinical settings. There was an apparent contradiction between placing a high value on personal health and believing that physicians ought to be available to patients at any time. Participants' satisfaction with the course bodes well for continual modification of such courses. Innovative flipped classroom format in combination with simulation-based sessions allows easy incorporation of contemporary professionalism issues surrounding social media.

Kin recognition, not competitive interactions, predicts root allocation in young Cakile edentula seedling pairs.

• Recent studies have demonstrated sibling vs stranger differences in group root allocation in plants, suggesting that plants have the potential for kin discrimination in competition. However, morphology differences could potentially be generated by competition-based mechanisms. Here, we tested these hypotheses for the sibling vs stranger differences in root allocation in Cakile edentula. • Seeds were planted in pairs of either kin (siblings) or strangers, from all combinations of eight families, to give eight kin (sibling) and 28 stranger pair identities. Because the species has a seed dimorphism, the 10 replicates of each pair identity included both seed types. Root allocation, size inequality between seedlings in a pair, and competitive ability were derived from measures of biomass and height. • Cakile edentula seedlings demonstrated the same kin recognition response previously observed in juvenile plants, with lower root allocation in kin pairs than stranger pairs. The seed dimorphism was not associated with root allocation. • The two competitive mechanisms, genetic differences in competitive ability and increased size inequality in stranger groups, did not explain the root allocation differences in these seedlings. Kin recognition offered the most probable explanation for the differences in root allocation between sibling and stranger pairs.